title: A randomized controlled trial of a vancomycin loading dose in children.
abstract: BACKGROUND
  Despite its frequent use, the optimal dosing regimen of intravenous vancomycin remains controversial. Achievement of therapeutic trough early in the course of illness may be beneficial. Our objective was to assess whether a loading dose of vancomycin would increase the proportion of children reaching target trough concentrations 8 hours after initiation of therapy.
  
  
  METHODS
  We enrolled hospitalized children aged 2-18 years prescribed vancomycin at Boston Children's Hospital between February 2011 and January 2012. Participants were randomized to receive a loading dose (30 mg/kg) or a conventional initial dose (20 mg/kg). These were followed by a 20 mg/kg/dose every 8 hours in both groups. Serum vancomycin concentrations were measured before the second and third doses. Pharmacokinetic parameters were calculated using individual and population pharmacokinetic models.
  
  
  RESULTS
  Two of nineteen (11%) loading dose recipients had a trough 15-20 mg/L before the second dose, compared with 0 of 27 in the conventional dose group (P=0.17). However, the median area under the curve/minimum inhibitory concentration estimates (for a hypothetical minimum inhibitory concentration=1 mg/L) were above 400 in both groups. Red man syndrome incidence was higher in loading dose recipients (48% vs. 24%, P=0.06).
  
  
  CONCLUSIONS
  A vancomycin loading dose did not result in earlier achievement of therapeutic trough concentrations in this study. However, the systemic exposure to vancomycin in children administered 60 mg/kg/day was adequate, despite lower than recommended measured trough levels. Therefore, the need for higher target trough concentrations should be questioned.
authors.affiliation: From the *Department of Medicine, Division of Infectious Diseases; †Clinical Pharmacology Research Program, Division of Emergency Medicine, Boston Children's Hospital, Boston, MA; ‡Division of Emergency Medicine; §Division of Clinical Pharmacology and Toxicology, The Hospital for Sick Children; ¶Department of Pharmacology and Toxicology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada; ‖Department of Pharmacy; and **Department of Laboratory Medicine, Boston Children's Hospital, Boston, MA.
authors.forename: Alicia
authors.initials: A
authors.lastname: Demirjian
authors.forename: Yaron
authors.initials: Y
authors.lastname: Finkelstein
authors.forename: Alejandro
authors.initials: A
authors.lastname: Nava-Ocampo
authors.forename: Alana
authors.initials: A
authors.lastname: Arnold
authors.forename: Sarah
authors.initials: S
authors.lastname: Jones
authors.forename: Michael
authors.initials: M
authors.lastname: Monuteaux
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Sandora
authors.forename: Al
authors.initials: A
authors.lastname: Patterson
authors.forename: Marvin B
authors.initials: MB
authors.lastname: Harper
mesh_terms: D000293:Adolescent; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D001424:Bacterial Infections / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism*; D016009:Chi-Square Distribution; D002648:Child; D002675:Child, Preschool; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D016903:Drug Monitoring; D005260:Female; D006760:Hospitalization; D006801:Humans; D008297:Male; D016896:Treatment Outcome; D014640:Vancomycin / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*
chemical_list: D000900:Anti-Bacterial Agents; D014640:Vancomycin